Defects in bone or osseous structures will initiate the process of bone healing. Healing often involves the replacement of injured tissue by connective tissue and leaves a scar. Bone, under optimal conditions, heals by regeneration in which injured tissues are replaced by their own kind and leaves no scar. The success of regeneration following injury depends, among other things, on the type of injury, the adequacy of treatment and the systemic health of the patient. Osseous repair involves at least six physiological stages: impact, induction, inflammation, soft callus formation, hard callus formation, remodeling and regeneration. Heppenstall, Fracture Treatment and Healing, W. B. Saunders, Philadelphia, 1980, page 35.
With inadequate treatment, severe injury and/or metabolic bone disease, fracture healing is significantly retarded. For example, in the case of a metabolic bone disease such as osteoporosis, 40% of patients with decreased bone mass due to osteoporosis showed a markedly impaired fracture repair rate. Only 33% of women in whom significant osteoporosis was present were able to achieve a solid union following femoral neck fractures. In comparison, a successful union was achieved in 90% of women having a physiologically normal bone mass a successful union was achieved. Lane et al., Osteoporosis, Orthopedics Clinics North America 15: 711 (1984); Arnold, J. Bone Joint Surg. 66A: 847 (1984); Scileppe et al., Surg. Form 32: 543 (1981).
Approximately 200,000 hip fractures in osteoporotic women occur in the United States annually. The women have a 40% mortality rate due to complications of repair of these fractures. As a result, there is a significant need to facilitate fracture repair in these types of patients. In addition, fractures in young accident and trauma victims result in loss of numerous productive days from the work place. For example, it takes an average of six weeks to repair even simple bone injuries in healthy individuals.
Bone fractures and bone wound healing following trauma or surgery account for considerable morbidity and mortality. For example, femoral neck fractures in patients under forty may be associated with avascular necrosis in as many as 40% of cases complicated by non-union. Kyle et al., Young Femoral Neck Fractures, (Abst.), Annual Meeting of American Academy of Orthopedic Surgery, Atlanta, Ga. (1984). Many other examples could be cited of the need for more expeditions methods to facilitate and/or accelerate repair of fracture or hard tissue defects.
Since the feasibility of the preparation of artificial cells was first demonstrated in 1957 by Chang (Chang, T. M. S. (1964) Science:146, 524), numerous approaches to their production and use have been evaluated. Artificial cell membranes have been reported using a variety of synthetic and biological materials to give the desired membrane properties. A large variety of materials can be enclosed (microencapsulated) in artificial cells. These include single and multienzyme systems, cell extracts, and combined enzyme-adsorbent systems (Chang, U.S. Pat. No. 4,642,120). One disadvantage of this prior art is based on the fact that these previous patents were based on the encapsulations of biological cells to prevent them from being adversely affected by external factors and immunological rejection (Chang, Biomedical Applications of Immobilized Enzymes and Proteins (Plenum: New York, 1977) Vols. 1 and 2; Mosbach et al. (1966) Acta Chem. Scan. 20: 2807; Lim et al. (1980) Science 210: 908). More recently, the microencapsulation of living biological cells that can be maintained in culture has been disclosed (Lim et al. (1980) Science 210: 908; U.S. Pat. No. 4,391,909). Unfortunately, the intent of past studies on the microencapsulation of living cells has focused on protecting these cells for storage. These previous studies on microencapsulated cells did not recognize the use of microencapsulation to facilitate the healing process.
Thus, there is a great need in the area of orthopedic medicine for compositions and methods of using microencapsulated living cells that will facilitate bone and heart tissue regeneration.